BGP-15 (66611-37-8) is a cellular protectant operating by several mechanisms. It is an insulin sensitizer1, HSP72 activator2, PARP inhibitor and ROS and lipid peroxidation reducer3. It protects mitochondria in acetaminophen-induced liver injury4 as well as LPS-induced destabilization5 and activates mitochondrial fusion6. Displays protective effects in heart failure7 and traumatic brain injury8 in animal models.
BGP 15 is a calcipotriene-based vitamin D3 analog that inhibits poly(ADP-ribose) polymerasesis (PARP), a class of enzymes that regulate DNA repair and apoptosis (1). BGP 15 is also a cardioprotective agent (2). Also, BPG 15 improves mitochondrial function, protects neurons from dying in vitro and in vivo, and promotes cardiac innervation in vivo.
previous study showed that bgp-15 at 200 μm could prevent the imatinib-induced oxidative damages, attenuate the depletion of high-energy phosphates, alter the signaling effect of imatinib by preventing p38 map kinase and jnk activation, and also induce the akt and gsk-3β phosphorylation [1].
in-vivo study indicated that bgp-15 improved cardiac function and reduced arrhythmic episodes in two hf and af mouse models. in these models, bgp-15 was associated with increased phosphorylation of igf1r. moreover, cardiac-specific igf1r transgenic overexpression in mice recapitulated the protection caused by bgp-15. the authors further demonstrated that bgp-15 with igf1r could provide protection independent of phosphoinositide 3-kinase-akt and heat-shock protein 70 [2].
Peto et al. (2020), Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome; Molecules 25 429
Henstridge et al. (2014), Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance; Diabetes 63 1881
Szabados et al. (2000), BGP-15, a nicotinic amidoxime derivative protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase; Biochem. Pharmacol. 59 937
Sarnyai et al. (2020), BGP-15 Protects Mitochondria in Acute Acetaminophen Overdose Induced Liver Injury; Pathol. Oncol. Res. 26 1797
Sumegi et al. (2017), BGP-15 Protects against Oxidative Stress- or Lipopolysaccharide-Induced Mitochondrial Destabilization and Reduces Mitochondrial Production of Reactive Oxygen Species; PLos One 12 e0169372
Szabo et al. (2018), Activation of mitochondrial fusion provides a new treatment for mitochondria-related diseases; Biochem. Pharmacol. 150 86
Sapra et al. (2014), The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice; Nat. Commun. 5 5705
Eroglu et al. (2014), Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury; J. Neurochem. 130 626
